Recombinant hirudin: clinical pharmacology and potential applications in nephrology

The last decade has been characterised by the development of several anticoagulation methods as alternatives to the heparins. One of these is the antithrombin hirudin, which is now available on a large scale in the recombinant form. The application of hirudin as an anticoagulant in haemodialysis has been complicated by the decrease of its clearance in patients with renal failure. The half-life of hirudin is more than 30 times longer in haemodialysis patients than in healthy subjects. Therefore, at present, its use in the haemodialysis setting is essentially limited to heparin-induced thrombocytopenia (HIT). Hirudin has been used sporadically and with success in nonrenal failure patients with HIT and at least once on a regular basis in a haemodialysis patient. A starting dose between 0.08 and 0.15 mg/kg for the first dialysis, followed by 50% of this quantity during the following dialyses is recommended. Hirudin activity can be monitored by aiming for threshold activated partial thromboplastin time (aPTT) values between 60 and 90 seconds, with urgent dosage adaptations once aPTT rises above 100 to 120 seconds. Hirudin concentrations during dialysis should be maintained between 400 and 1000 microg/L, with determination by ecarin clotting time or chromogenic assays. At present, the use of hirudin is also limited by the absence of an effective antidote. In studies in humans, no enhanced removal of hirudin was observed during dialysis with large pore dialysers in contrast to earlier published animal studies.